P1334: THE IMPACT OF IMMUNOSUPPRESSION ON RECONSTITUTION OF CMV-SPECIFIC T CELLS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: A. Dmitrova, M. Drokov, T. Tupoleva, D. Tikhomirov, L. Kuzmina, M. Vagida, G. Efimov, E. Parovichnikova
Journal: HemaSphere (2022)

Background: Cytomegalovirus infection (CMV infection) is the most frequent and life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The development of CMV infection is controlled by T-cell immunity. The type of the immunosuppressive regimen is the most important reason of decreased CMV-specific CD8+ immune response following allo-HSCT. Aims: In our study we try to assess the influence of different types of immunosuppressive regimens on recovery of the CMV-specific CD8+ T cells in patients after allo-HSCT. Methods: Analysis of peripheral blood CMV-specific CD8+ T cells from 108 patients performed by flow cytometry at + 30, +90, +180 days after allo-HSCT. We used fluorochrome-labeled monoclonal antibodies against CD3, CD8, CD45 molecules, viability reagent and tetramers which were formed from MHC class I monomers loaded with immunodominant epitopes of cytomegalovirus pp65 protein (HLA-A*0201/NLV, HLA-B*0702/TPR, HLA-B*0702/RPH) and Streptavidin, R-Phycoerythrin conjugate (SAPE). For graft-versus-host disease (GVHD) prophylaxis 22 (20,3%) patients received anti-thymocyte globulin (ATG), 52 (48,2%) – posttransplant cyclophosphamide (PT-Cy), 12 (11,1%) – ATG + PT-Cy, 13 (12%) – T-cell depletion protocol and 9 (8,4%) patients received other immunosuppressive regimens. Detailed patients' characteristics are presented in Table 1. Table 1. - Patients' characteristics (n=108). Gender, n (%) Female 62 (57,4 %) Male 46 (42,6 %) Age, Median (IQR) 36 (28 – 43) Diagnosis, n (%) Aplastic anemia 1 (0,93 %) Lymphoma 3 (2,78 %) Myelodysplastic syndrome (MDS) 13 (12,04 %) Acute lymphoblastic leukemia (ALL) 37 (34,26 %) Acute myeloid leukemia (AML) 49 (45,37 %) Primary myelofibrosis 1 (0,93 %) Chronic lymphocytic leukemia (CLL) 1 (0,93 %) Chronic myelogenous leukemia (CML) 2 (1,85 %) Chronic myelomonocytic leukemia (CMML) 1 (0,93 %) Conditioning regimen, n (%) Myeloablative conditioning regimen (MAC) 15 (13,89 %) Reduced intensity conditioning regimen (RIC) 93 (86,11 %) Graft source, n (%) Bone marrow 21 (19,44 %) Peripheral blood stem cells 87 (80,56 %) Results: The data shown in figure 1 indicate that the use of PT-Cy (PT-Cy 50 mg/kg/day intravenously on days +3, +4) and T-cell depletion protocols as GVHD prophylaxis leads to lower CMV-specific T cells counts during 6-months follow-up period after allo-HSCT. The combination of PT-Cy and ATG also shows reduced absolute numbers of CMV-specific CD8+ T cells compared to ATG protocols (ATG 40 mg/kg/day intravenously for 4 days). Image:Summary/Conclusion: Our results show that patients who received PT-Cy as GVHD prophylaxis and T-cell depletion-grafts have highest risk for developing CMV infection after allo-HSCT. The management of CMV infection by monitoring of CMV by polymerase chain reaction, use of antiviral prophylaxis and prompt use of pre-emptive therapy are very important for such patients' groups.